Table 1 The role of LDLR in several viral infections

HCV

The LDLR has been suggested to facilitate the entrance of HCV into cells. It has been established that the expression of the LDLR gene in human mononuclear cells is coordinated and synchronized with that of the gene in the human liver. A correlation between LDLR expression and HCV viral load may indicate that the LDLR is involved in the HCV replication cycle in human subjects.

[35]

HBV

LDLR binds to the apoE associated with HBV and functions as an HBV cell attachment receptor. When administered during HBV infection, but not subsequently, the LDLR-blocking monoclonal antibody C7 suppressed HBV infection, indicating that its activity happened very early in the HBV infection process.

[36]

SARS-CoV-2

Lentiviral pseudovirions coated with SARS-CoV-2 spike protein can enter ARPE-19, a human retinal pigment epithelium cell line, in a laboratory setting. This entry process can be hindered by specific antibodies, cholesterol-depleting agents, and siRNAs targeting LDLR. Researchers’ hypothesis suggests that caveolae and LDLR receptors within caveolae play a role in the receptor-mediated endocytosis mechanism utilized by the SARS-CoV-2 virus to infect particular tissues, such as ocular cells.

[37]

HIV

LDLR levels in mononuclear cells of the liver and blood are down-regulated in HIV-positive patients with lipodystrophy, independent of PI-ART, compared to HIV-negative controls and positive patients without lipodystrophy.

[38, 39]

Dengue virus

For DENV to proliferate and be introduced, cholesterol is essential. Furthermore, it was shown that soon after infection, there was an increase in lipid raft formation and total cholesterol levels. This improvement is linked to decreased HMGCR phosphorylation and increased LDLR levels on the surface of infected Huh-7 cells.

[40]

Crimean-Congo hemorrhagic fever virus (CCHFV)

The LDLR is an essential entry receptor for CCHFV infection. By employing biochemical, cellular, and genetic methodologies, we provide evidence that CCHFV Gc forms a direct association with LDLR, a critical factor in facilitating its entry into diverse cell types ranging from mouse to human, and ensuring successful infection and pathogenesis in mice.

[41]

Zika (ZIKV), Yellow Fever (YFV),

and West Nile (WNV) virus

By manipulating host cholesterol levels during infection with DENV, ZIKV, YFV, and WNV, interferon type I response regulation, viral entry, and the assembly, egress, and formation of replicative complexes are all enhanced. Virus particles establish a connection with the cell surface and bind to receptors located in lipid rafts, which are cholesterol-rich microdomains of the plasma membrane. This procedure initiates endocytosis dependent on clathrin. Upon attachment and entry, the infected cell’s surface demonstrates an immediate increase in cholesterol levels, associated with a rise in LDLR.

[42]